Prosthetic heart valve

ABSTRACT

Embodiments of a radially collapsible and expandable prosthetic heart valve and method for crimping the prosthetic heart valve are disclosed. A method of radially compressing a prosthetic valve can include partially inserting the valve while in a radially expanded configuration into a crimping device comprising crimper jaws, wherein a portion of the valve comprising an outer skirt extends outside of the crimper jaws. The method can further include crimping the valve to a first partially collapsed configuration, further inserting the valve into the crimping device, such that the outer skirt is between the crimper jaws, and crimping the valve to a second partially collapsed configuration, wherein a diameter of the valve is smaller in the second partially collapsed configuration than in the first partially collapsed configuration.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.16/262,188, filed Jan. 30, 2019, which is a continuation of U.S. patentapplication Ser. No. 14/704,861, filed May 5, 2015, now U.S. Pat. No.10,195,025, which claims the benefit of U.S. Provisional Application No.61/991,904, filed May 12, 2014, each of which is incorporated byreference herein in its entirety.

FIELD

The present disclosure relates to implantable expandable prostheticdevices and to methods for crimping a prosthetic device.

BACKGROUND

The human heart can suffer from various valvular diseases. Thesevalvular diseases can result in significant malfunctioning of the heartand ultimately require replacement of the native valve with anartificial valve. There are a number of known artificial valves and anumber of known methods of implanting these artificial valves in humans.Because of the drawbacks associated with conventional open-heartsurgery, percutaneous and minimally-invasive surgical approaches aregarnering intense attention. In one technique, a prosthetic valve isconfigured to be implanted in a much less invasive procedure by way ofcatheterization. For example, collapsible transcatheter prosthetic heartvalves can be crimped to a compressed state and percutaneouslyintroduced in the compressed state on a catheter and expanded to afunctional size at the desired position by balloon inflation or byutilization of a self-expanding frame or stent.

A prosthetic valve for use in such a procedure can include a radiallycollapsible and expandable frame to which leaflets of the prostheticvalve can be coupled. For example, U.S. Pat. Nos. 6,730,118, 7,393,360,7,510,575, and 7,993,394, which are incorporated herein by reference,describe exemplary collapsible transcatheter prosthetic heart valves.

A prosthetic valve for use in such a procedure can include a radiallycollapsible and expandable frame to which leaflets of the prostheticvalve can be coupled, and which can be percutaneously introduced in acollapsed configuration on a catheter and expanded in the desiredposition by balloon inflation or by utilization of a self-expandingframe or stent. A challenge in catheter-implanted prosthetic valves iscontrol of perivalvular leakage around the valve, which can occur for aperiod of time following initial implantation. An additional challengeincludes the process of crimping such a prosthetic valve to a profilesuitable for percutaneous delivery to a subject, as well as for storageand/or delivery to a health care provider.

SUMMARY

Embodiments of a radially collapsible and expandable prosthetic valveare disclosed herein that include an improved outer skirt forcontrolling perivalvular leakage, as well as methods of crimping, andapparatuses including, such prosthetic valves. In several embodiments,the disclosed prosthetic valves are configured as replacement heartvalves for implantation into a subject.

In several embodiments, a radially compressible and expandableprosthetic heart valve is provided comprising an annular frame having aninflow end portion and an outflow end portion, a leaflet structurepositioned within the frame, and an annular outer skirt positionedaround an outer surface of the frame. The outer skirt comprises aninflow edge radially secured to the frame at a first location, anoutflow edge radially secured to the frame at a second location, and anintermediate portion between the inflow edge and the outflow edge. Theintermediate portion of the outer skirt comprises slack that buckles orbillows radially outward from the inflow and outflow edges of the outerskirt when the prosthetic valve is in the expanded configuration. Whenthe prosthetic valve is collapsed to the collapsed configuration, theaxial distance between the inflow edge of the outer skirt and theoutflow edge of the outer skirt increases, reducing the slack in theintermediate portion of the outer skirt. The outer skirt can compriseone of (a) a fabric that is stiffer in the axial direction of the valvecompared to a circumferential direction to enhance the radial outwardbuckling of the slack, and/or (b) a self-expandable fabric comprisingfibers made of shape memory material having a shape memory set toenhance the radially outward buckling of the slack of the outer skirt.

In embodiments wherein the outer skirt comprises the fabric that isstiffer in the axial direction of the valve compared to acircumferential direction, the outer skirt can comprise a weave of afirst set of fibers parallel with the axial direction of the prostheticvalve and a second set of fibers perpendicular to the axial direction ofthe prosthetic valve. In some embodiments, the fibers in the first setof fibers are stiffer than the fibers in the second set of fibers. Thefirst set of fibers can comprise a set of monofilament fibers. Thesecond set of fibers can comprise a set of microfilament fibers, a setof multifilament fibers, or a set of a microfilament fibers andmultifilament fibers. In further embodiments, the second set of fiberscomprises fibers that do not comprise residual strain after theprosthetic valve is expanded to the expanded configuration from thecollapsed configuration.

In embodiments wherein the outer skirt comprises the self-expandablefabric comprising fibers made of shape memory material, theself-expandable fabric can comprise a weave of warp fibers and weftfibers, wherein one or more of the weft fibers comprise the fibers madeof shape memory material. The weave of warp and weft fibers can comprisea combination of multiple weave patters. For example, the weave of warpand weft fibers can comprise a combination of a plain weave patterncomprising warp fibers and weft fibers made of non-shape memorymaterial, and a satin weave pattern comprising warp fibers made ofnon-shape memory material and weft fibers made of the shape memorymaterial. In some embodiments, the shape memory material can be a nickeltitanium alloy, for example, the fibers made of the shape memorymaterial can be nickel titanium wires comprising a diameter of from 0.5to 15 Mils.

An exemplary embodiment of an assembly for implanting a prosthetic heartvalve in a patient's body comprises a delivery apparatus comprising anelongated shaft and a radially expandable prosthetic heart valve mountedon the shaft in a radially collapsed configuration for delivery into thebody.

In some embodiments, a method of crimping a prosthetic valve comprisespartially inserting the prosthetic valve in the expanded configurationinto the crimping jaws of a crimping device, wherein a portion of theprosthetic valve comprising an outer skirt extends outside of thecrimper jaws. The prosthetic valve is then crimped to a first partiallycollapsed configuration, after which the prosthetic valve is fullyinserted into the jaws of the crimping device. The prosthetic valve isthen crimped to a second partially collapsed configuration, andoptionally crimped to a fully collapsed configuration, before removalfrom the crimping device.

The foregoing and other features and advantages of this disclosure willbecome more apparent from the following detailed description of severalembodiments which proceeds with reference to the accompanying figures.

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1-3 show an exemplary embodiment of a prosthetic heart valve.

FIGS. 4-10 show an exemplary frame of the prosthetic heart valve of FIG.1.

FIGS. 11-15B show another exemplary frame for use in a prosthetic heartvalve.

FIGS. 16A and 16B show an exemplary inner skirt of the prosthetic heartvalve of FIG. 1.

FIG. 17 shows another embodiment of a prosthetic heart valve with adeformed frame.

FIG. 18 shows the prosthetic heart valve of FIG. 1 in a collapsedconfiguration and mounted on an exemplary balloon catheter.

FIGS. 19A, 19B, and 20 show the assembly of the inner skirt of FIG. 16Awith the frame of FIG. 4.

FIGS. 21-28 show the assembly of an exemplary leaflet structure.

FIGS. 29-35 show the assembly of commissure portions of the leafletstructure with window frame portions of the frame.

FIGS. 36-40 show the assembly of the leaflet structure with the innerskirt along a lower edge of the leaflets.

FIG. 41 shows a flattened view of an exemplary outer skirt.

FIGS. 42 and 43 show the exemplary prosthetic heart valve of FIG. 1.

FIG. 44 shows a portion of an outer skirt fabric, detailing warp andweft fibers.

FIG. 45 shows a portion of the frame of FIG. 4 in a radially collapsedconfiguration.

FIG. 46 shows a cross-sectional profile of the frame of FIG. 4, showingsa general tapering from the outflow end to the inflow end.

FIG. 47 shows the frame of FIG. 4 in an unrolled, flat configuration.

FIG. 48 shows the prosthetic heart valve of FIG. 1 in a collapsedconfiguration and mounted on an exemplary balloon catheter.

FIGS. 49-51 show balloon expansion of an alternative embodiment of aframe for a prosthetic valve having inflow and outflow end portions ofreduced thickness.

FIG. 52 illustrates a process for crimping an expandable and collapsibleprosthetic valve including an outer skirt.

FIGS. 53-56 illustrate a process for crimping an expandable andcollapsible prosthetic valve including an outer skirt.

FIG. 57 shows a portion of an outer skirt fabric, detailing warp andweft fibers.

FIGS. 58-60 show a set of diagrams illustrating a portion of an outerskirt fabric, detailing the design of three different patterns of warpand weft fibers.

DETAILED DESCRIPTION

For purposes of this description, certain aspects, advantages, and novelfeatures of the embodiments of this disclosure are described herein. Thedescribed methods, systems, and apparatus should not be construed aslimiting in any way. Instead, the present disclosure is directed towardall novel and nonobvious features and aspects of the various disclosedembodiments, alone and in various combinations and sub-combinations withone another. The disclosed methods, systems, and apparatus are notlimited to any specific aspect, feature, or combination thereof, nor dothe disclosed methods, systems, and apparatus require that any one ormore specific advantages be present or problems be solved.

Features, integers, characteristics, compounds, chemical moieties, orgroups described in conjunction with a particular aspect, embodiment orexample of the invention are to be understood to be applicable to anyother aspect, embodiment or example described herein unless incompatibletherewith. All of the features disclosed in this specification(including any accompanying claims, abstract, and drawings), and/or allof the steps of any method or process so disclosed, may be combined inany combination, except combinations where at least some of suchfeatures and/or steps are mutually exclusive. The invention is notrestricted to the details of any foregoing embodiments. The inventionextends to any novel one, or any novel combination, of the featuresdisclosed in this specification (including any accompanying claims,abstract, and drawings), or to any novel one, or any novel combination,of the steps of any method or process so disclosed.

Although the operations of some of the disclosed methods are describedin a particular, sequential order for convenient presentation, it shouldbe understood that this manner of description encompasses rearrangement,unless a particular ordering is required by specific language set forthbelow. For example, operations described sequentially may in some casesbe rearranged or performed concurrently. Moreover, for the sake ofsimplicity, the attached figures may not show the various ways in whichthe disclosed methods, systems, and apparatus can be used in conjunctionwith other systems, methods, and apparatus.

As used herein, the terms “a”, “an”, and “at least one” encompass one ormore of the specified element. That is, if two of a particular elementare present, one of these elements is also present and thus “an” elementis present. The terms “a plurality of” and “plural” mean two or more ofthe specified element.

As used herein, the term “and/or” used between the last two of a list ofelements means any one or more of the listed elements. For example, thephrase “A, B, and/or C” means “A”, “B”, “C”, “A and B”, “A and C”, “Band C”, or “A, B, and C”.

As used herein, the term “coupled” generally means physically coupled orlinked and does not exclude the presence of intermediate elementsbetween the coupled items absent specific contrary language.

FIGS. 1-3 show various views of a prosthetic heart valve 10, accordingto one embodiment. The illustrated prosthetic valve is adapted to beimplanted in the native aortic annulus, although in other embodiments itcan be adapted to be implanted in the other native annuluses of theheart (e.g., the pulmonary, mitral, and tricuspid valves). Theprosthetic valve can also be adapted to be implanted in other tubularorgans or passageways in the body. The prosthetic valve 10 can have fourmain components: a stent, or frame, 12, a valvular structure 14, aninner skirt 16, and a perivalvular sealing means, and can have an inflowend portion 15, an intermediate portion 17, and an outflow end portion19. In the illustrated embodiment, the perivalvular sealing meanscomprises an outer skirt 18.

The valvular structure 14 can comprise three leaflets 40, collectivelyforming a leaflet structure, which can be arranged to collapse in atricuspid arrangement, as best shown in FIG. 2. The lower edge ofleaflet structure 14 desirably has an undulating, curved scalloped shape(suture line 154 shown in FIG. 1 tracks the scalloped shape of theleaflet structure). By forming the leaflets with this scallopedgeometry, stresses on the leaflets are reduced, which in turn improvesdurability of the prosthetic valve. Moreover, by virtue of the scallopedshape, folds and ripples at the belly of each leaflet (the centralregion of each leaflet), which can cause early calcification in thoseareas, can be eliminated or at least minimized. The scalloped geometryalso reduces the amount of tissue material used to form leafletstructure, thereby allowing a smaller, more even crimped profile at theinflow end of the prosthetic valve. The leaflets 40 can be formed ofpericardial tissue (e.g., bovine pericardial tissue), biocompatiblesynthetic materials, or various other suitable natural or syntheticmaterials as known in the art and described in U.S. Pat. No. 6,730,118,which is incorporated by reference herein.

The bare frame 12 is shown in FIG. 4. The frame 12 can be formed with aplurality of circumferentially spaced slots, or commissure windows, 20(three in the illustrated embodiment) that are adapted to mount thecommissures of the valvular structure 14 to the frame, as described ingreater detail below. The frame 12 can be made of any of varioussuitable plastically-expandable materials (e.g., stainless steel, etc.)or self-expanding materials (e.g., nickel titanium alloy (NiTi), such asnitinol) as known in the art. When constructed of aplastically-expandable material, the frame 12 (and thus the prostheticvalve 10) can be crimped to a radially collapsed configuration on adelivery catheter and then expanded inside a patient by an inflatableballoon or equivalent expansion mechanism. When constructed of aself-expandable material, the frame 12 (and thus the prosthetic valve10) can be crimped to a radially collapsed configuration and restrainedin the collapsed configuration by insertion into a sheath or equivalentmechanism of a delivery catheter. Once inside the body, the prostheticvalve can be advanced from the delivery sheath, which allows theprosthetic valve to expand to its functional size.

Suitable plastically-expandable materials that can be used to form theframe 12 include, without limitation, stainless steel, a biocompatible,high-strength alloys (e.g., a cobalt-chromium or anickel-cobalt-chromium alloys), polymers, or combinations thereof. Inparticular embodiments, frame 12 is made of anickel-cobalt-chromium-molybdenum alloy, such as MP35N® alloy (SPSTechnologies, Jenkintown, Pa.), which is equivalent to UNS R30035 alloy(covered by ASTM F562-02). MP35N® alloy/UNS R30035 alloy comprises 35%nickel, 35% cobalt, 20% chromium, and 10% molybdenum, by weight. It hasbeen found that the use of MP35N® alloy to form frame 12 providessuperior structural results over stainless steel. In particular, whenMP35N® alloy is used as the frame material, less material is needed toachieve the same or better performance in radial and crush forceresistance, fatigue resistances, and corrosion resistance. Moreover,since less material is required, the crimped profile of the frame can bereduced, thereby providing a lower profile prosthetic valve assembly forpercutaneous delivery to the treatment location in the body.

Referring to FIGS. 4 and 5, the frame 12 in the illustrated embodimentcomprises a first, lower row I of angled struts 22 arranged end-to-endand extending circumferentially at the inflow end of the frame; a secondrow II of circumferentially extending, angled struts 24; a third row IIIof circumferentially extending, angled struts 26; a fourth row IV ofcircumferentially extending, angled struts 28; and a fifth row V ofcircumferentially extending, angled struts 32 at the outflow end of theframe. A plurality of substantially straight axially extending struts 34can be used to interconnect the struts 22 of the first row I with thestruts 24 of the second row II. The fifth row V of angled struts 32 areconnected to the fourth row IV of angled struts 28 by a plurality ofaxially extending window frame portions 30 (which define the commissurewindows 20) and a plurality of axially extending struts 31. Each axialstrut 31 and each frame portion 30 extends from a location defined bythe convergence of the lower ends of two angled struts 32 to anotherlocation defined by the convergence of the upper ends of two angledstruts 28. FIGS. 6, 7, 8, 9, and 10 are enlarged views of the portionsof the frame 12 identified by letters A, B, C, D, and E, respectively,in FIG. 4.

Each commissure window frame portion 30 mounts a respective commissureof the leaflet structure 14. As can be seen each frame portion 30 issecured at its upper and lower ends to the adjacent rows of struts toprovide a robust configuration that enhances fatigue resistance undercyclic loading of the prosthetic valve compared to known, cantileveredstruts for supporting the commissures of the leaflet structure. Thisconfiguration enables a reduction in the frame wall thickness to achievea smaller crimped diameter of the prosthetic valve. In particularembodiments, the thickness T of the frame 12 (FIG. 4) measured betweenthe inner diameter and outer diameter is about 0.48 mm or less.

The struts and frame portions of the frame collectively define aplurality of open cells of the frame. At the inflow end of the frame 12,struts 22, struts 24, and struts 34 define a lower row of cells definingopenings 36. The second, third, and fourth rows of struts 24, 26, and 28define two intermediate rows of cells defining openings 38. The fourthand fifth rows of struts 28 and 32, along with frame portions 30 andstruts 31, define an upper row of cells defining openings 40. Theopenings 40 are relatively large and are sized to allow portions of theleaflet structure 14 to protrude, or bulge, into and/or through theopenings 40 when the frame 12 is crimped in order to minimize thecrimping profile.

As best shown in FIG. 7, the lower end of the strut 31 is connected totwo struts 28 at a node or junction 44, and the upper end of the strut31 is connected to two struts 32 at a node or junction 46. The strut 31can have a thickness S1 that is less than the thicknesses S2 of thejunctions 44, 46. FIG. 45 shows a portion of the frame 12 in a collapsedconfiguration. The junctions 44, 46, along with junctions 64, preventfull closure of openings 40. FIG. 18 shows the prosthetic valve 10crimped on a balloon catheter. As can be seen, the geometry of thestruts 31, and junctions 44, 46, and 64 assists in creating enough spacein openings 40 in the collapsed configuration to allow portions of theprosthetic leaflets to protrude or bulge outwardly through openings.This allows the prosthetic valve to be crimped to a relatively smallerdiameter than if all of the leaflet material were constrained within thecrimped frame.

The frame 12 is configured to reduce, to prevent, or to minimizepossible over-expansion of the prosthetic valve at a predeterminedballoon pressure, especially at the outflow end portion 19 of the frame,which supports the leaflet structure 14. In one aspect, the frame isconfigured to have relatively larger angles 42 a, 42 b, 42 c, 42 d, 42 ebetween struts, as shown in FIG. 5. The larger the angle, the greaterthe force required to open (expand) the frame. This phenomenon isschematically illustrated in FIGS. 15A and 15B. FIG. 15A shows a strut32 when the frame 12 is in its collapsed configuration (e.g., mounted ona balloon). The vertical distance d₁ between the ends of the struts isgreatest when the frame is compressed, providing a relatively largemoment between forces F₁ and F₂ acting on the ends of the strut inopposite directions upon application of an opening force from inflationof the balloon (or from expansion of another expansion device). When theframe expands radially, the vertical distance between the ends of thestrut decreases to a distance d₂, as depicted in FIG. 15B. As thevertical distance decreases, so does the moment between forces F₁ andF₂. Hence, it can be seen that a relatively greater expansion force isrequired as the vertical distance and the moment between the ends of thestrut decreases. Moreover, strain hardening (stiffening) at the ends ofthe strut increases as the frame expands, which increases the expansionforce required to induce further plastic deformation at the ends of thestrut. As such, the angles between the struts of the frame can beselected to limit radial expansion of the frame at a given openingpressure (e.g., inflation pressure of the balloon). In particularembodiments, these angles are at least 110 degrees or greater when theframe is expanded to its functional size, and even more particularlythese angles are up to about 120 degrees when the frame is expanded toits functional size.

In addition, the inflow and outflow ends of a frame generally tend toover-expand more so than the middle portion of the frame due to the “dogboning” effect of the balloon used to expand the prosthetic valve. Toprotect against over-expansion of the leaflet structure 14, the leafletstructure desirably is secured to the frame 12 below the upper row ofstruts 32, as best shown in FIG. 1. FIG. 47 shows a flattened view ofthe frame 12 similar to FIG. 5, but showing a dashed line 176superimposed over the frame to indicate the approximate position of theupper edges of the leaflets 40 in some embodiments. Thus, in the eventthat the outflow end of the frame is over-expanded, the leafletstructure is positioned at a level below where over-expansion is likelyto occur, thereby protecting the leaflet structure from over-expansion.

In a known prosthetic valve construction, portions of the leaflets canprotrude longitudinally beyond the outflow end of the frame when theprosthetic valve is crimped if the leaflets are mounted too close to thedistal end of the frame. If the delivery catheter on which the crimpedprosthetic valve is mounted includes a pushing mechanism or stop memberthat pushes against or abuts the outflow end of the prosthetic valve(for example, to maintain the position of the crimped prosthetic valveon the delivery catheter), the pushing member or stop member can damagethe portions of the exposed leaflets that extend beyond the outflow endof the frame. Another benefit of mounting the leaflets at a locationspaced away from the outflow end of the frame is that when theprosthetic valve is crimped on a delivery catheter, as shown in FIG. 48,the outflow end of the frame 12 rather than the leaflets 40 is theproximal-most component of the prosthetic valve 10. As such, if thedelivery catheter includes a pushing mechanism or stop member thatpushes against or abuts the outflow end of the prosthetic valve, thepushing mechanism or stop member contacts the outflow end of the frame,and not leaflets 40, so as to avoid damage to the leaflets.

Also, as can be seen in FIG. 5, the openings 36 of the lowermost row ofopenings in the frame are relatively larger than the openings 38 of thetwo intermediate rows of openings. As shown in FIG. 46, this allows theframe, when crimped, to assume an overall tapered shape that tapers froma maximum diameter D₁ at the outflow end of the prosthetic valve to aminimum diameter D₂ at the inflow end of the prosthetic valve. Whencrimped, the frame 12 has a reduced diameter region extending along aportion of the frame adjacent the inflow end of the frame, indicated byreference number 174, that generally corresponds to the region of theframe covered by the outer skirt 18. In some embodiments, the diameterof region 174 is reduced compared to the diameter of the upper portionof the frame (which is not covered by the outer skirt) such that theouter skirt 18 does not increase the overall crimp profile of theprosthetic valve. When the prosthetic valve is deployed, the frame canexpand to the generally cylindrical shape shown in FIG. 4. In oneexample, the frame of a 26-mm prosthetic valve, when crimped, had adiameter D₁ of 14 French at the outflow end of the prosthetic valve anda diameter D₂ of 12 French at the inflow end 174 of the prostheticvalve.

FIGS. 11 and 12 show an alternative frame 50 that can be incorporated inthe prosthetic valve 10. The frame 50 comprises multiple rows ofcircumferentially extending, angled struts 52 that are connected to eachother at nodes, or connecting portions, 54 and 56. The uppermost row ofstruts 52 are connected to an adjacent row of struts by a plurality ofaxially extending struts 58 and commissure window frame portions 60.Each commissure frame portion 60 defines a slot, or commissure window,62 for mounting a respective commissure of the valvular structure, asdescribed in greater detail below. In particular embodiments, thethickness T of the frame 50 is about 0.45 mm or less. Of course, thethickness T of the frame is selected to provide sufficient strength tothe frame. As such, those skilled in the art will understand that thethickness T differs for different sub-components and/or assemblies ofthe frame in some embodiments. FIGS. 13 and 14 are enlarged views of theportions of the frame 50 identified by letters A and B, respectively, inFIG. 12.

The main functions of the inner skirt 16 are to assist in securing thevalvular structure 14 to the frame 12 and to assist in forming a goodseal between the prosthetic valve and the native annulus by blocking theflow of blood through the open cells of the frame 12 below the loweredge of the leaflets. The inner skirt 16 desirably comprises a tough,tear resistant material such as polyethylene terephthalate (PET),although various other synthetic or natural materials can be used. Thethickness of the skirt desirably is less than about 0.15 mm (about 6mil), and desirably less than about 0.1 mm (about 4 mil), and even moredesirably about 0.05 mm (about 2 mil). In particular embodiments, theskirt 16 can have a variable thickness, for example, the skirt can bethicker at least one of its edges than at its center. In oneimplementation, the skirt 16 can comprise a PET skirt having a thicknessof about 0.07 mm at its edges and about 0.06 mm at its center. Thethinner skirt can provide for better crimping performances while stillproviding good perivalvular sealing.

The skirt 16 can be secured to the inside of frame 12 via sutures 70, asshown in FIG. 39. Valvular structure 14 can be attached to the skirt viaone or more reinforcing strips 72 (which collectively can form asleeve), for example thin, PET reinforcing strips, discussed below,which enables a secure suturing and protects the pericardial tissue ofthe leaflet structure from tears. Valvular structure 14 can besandwiched between skirt 16 and the thin PET strips 72 as shown in FIG.38. Sutures 154, which secure the PET strip and the leaflet structure 14to skirt 16, can be any suitable suture, such as Ethibond Excel® PETsuture (Johnson & Johnson, New Brunswick, N.J.). Sutures 154 desirablytrack the curvature of the bottom edge of leaflet structure 14, asdescribed in more detail below.

Known fabric skirts comprise a weave of warp and weft fibers that extendperpendicularly to each other and with one set of the fibers extendinglongitudinally between the upper and lower edges of the skirt. When themetal frame to which the fabric skirt is secured is radially compressed,the overall axial length of the frame increases. Unfortunately, a fabricskirt, which inherently has limited elasticity, cannot elongate alongwith the frame and therefore tends to deform the struts of the frame andto prevent uniform crimping.

Referring to FIG. 16B, in contrast to known fabric skirts, the skirt 16desirably is woven from a first set of fibers, or yarns or strands, 78and a second set of fibers, or yarns or strands, 80, both of which arenon-perpendicular to the upper edge 82 and the lower edge 84 of theskirt. In particular embodiments, the first set of fibers 78 and thesecond set of fibers 80 extend at angles of about 45 degrees relative tothe upper and lower edges 82, 84. The skirt 16 can be formed by weavingthe fibers at 45 degree angles relative to the upper and lower edges ofthe fabric. Alternatively, the skirt can be diagonally cut (cut on abias) from a vertically woven fabric (where the fibers extendperpendicularly to the edges of the material) such that the fibersextend at 45 degree angles relative to the cut upper and lower edges ofthe skirt. As further shown in FIG. 16B, the opposing short edges 86, 88of the skirt desirably are non-perpendicular to the upper and loweredges 82, 84. For example, the short edges 86, 88 desirably extend atangles of about 45 degrees relative to the upper and lower edges andtherefore are aligned with the first set of fibers 78. Therefore theoverall general shape of the skirt is that of a rhomboid orparallelogram.

FIG. 17 shows an example of a crimped prosthetic valve where the strutshave been deformed in several locations, as indicated by referencenumber 100, by a skirt having fibers that extend perpendicular to and/orlongitudinally between the upper and lower edges of the skirt. Moreover,the fabric tends to bunch or create bulges of excess material in certainlocations, which limits the minimum crimping profile and preventsuniform crimping.

FIGS. 19A and 19B show the skirt 16 after opposing short edge portions90, 92 have been sewn together to form the annular shape of the skirt.As shown, the edge portion 90 can be placed in an overlappingrelationship relative to the opposite edge portion 92, and the two edgeportions can be sewn together with a diagonally extending suture line 94that is parallel to short edges 86, 88. The upper edge portion of theskirt 16 can be formed with a plurality of projections 96 that define anundulating shape that generally follows the shape or contour of thefourth row of struts 28 immediately adjacent the lower ends of axialstruts 31. In this manner, as best shown in FIG. 20, the upper edge ofskirt 16 can be tightly secured to struts 28 with sutures 70. Skirt 16can also be formed with slits 98 to facilitate attachment of the skirtto the frame. Slits 98 are dimensioned so as to allow an upper edgeportion of skirt to be partially wrapped around struts 28 and to reducestresses in the skirt during the attachment procedure. For example, inthe illustrated embodiment, skirt 16 is placed on the inside of frame 12and an upper edge portion of the skirt is wrapped around the uppersurfaces of struts 28 and secured in place with sutures 70. Wrapping theupper edge portion of the skirt around struts 28 in this manner providesfor a stronger and more durable attachment of the skirt to the frame.The skirt 16 can also be secured to the first, second, and third rows ofstruts 22, 24, and 26, respectively, with sutures 70.

Referring again to FIG. 16B, due to the angled orientation of the fibersrelative to the upper and lower edges, the skirt can undergo greaterelongation in the axial direction (i.e., in a direction from the upperedge 82 to the lower edge 84).

Thus, when the metal frame 12 is crimped (as shown in FIG. 18), theskirt 16 can elongate in the axial direction along with the frame andtherefore provide a more uniform and predictable crimping profile. Eachcell of the metal frame in the illustrated embodiment includes at leastfour angled struts that rotate towards the axial direction on crimping(e.g., the angled struts become more aligned with the length of theframe). The angled struts of each cell function as a mechanism forrotating the fibers of the skirt in the same direction of the struts,allowing the skirt to elongate along the length of the struts. Thisallows for greater elongation of the skirt and avoids undesirabledeformation of the struts when the prosthetic valve is crimped.

In addition, the spacing between the woven fibers or yarns can beincreased to facilitate elongation of the skirt in the axial direction.For example, for a PET skirt 16 formed from 20-denier yarn, the yarndensity can be about 15% to about 30% lower than in a typical PET skirt.In some examples, the yarn spacing of the skirt 16 can be from about 60yarns per cm (about 155 yarns per inch) to about 70 yarns per cm (about180 yarns per inch), such as about 63 yarns per cm (about 160 yarns perinch), whereas in a typical PET skirt the yarn spacing can be from about85 yarns per cm (about 217 yarns per inch) to about 97 yarns per cm(about 247 yarns per inch). The oblique edges 86, 88 promote a uniformand even distribution of the fabric material along inner circumferenceof the frame during crimping so as to reduce or minimize bunching of thefabric to facilitate uniform crimping to the smallest possible diameter.Additionally, cutting diagonal sutures in a vertical manner may leaveloose fringes along the cut edges. The oblique edges 86, 88 helpminimize this from occurring. As noted above, FIG. 17 shows a crimpedprosthetic valve with a typical skirt that has fibers that runperpendicularly to the upper and lower edges of the skirt. ComparingFIGS. 17 and 18, it is apparent that the construction of skirt 16 avoidsundesirable deformation of the frame struts and provides more uniformcrimping of the frame.

In alternative embodiments, the skirt can be formed from woven elasticfibers that can stretch in the axial direction during crimping of theprosthetic valve. The warp and weft fibers can run perpendicularly andparallel to the upper and lower edges of the skirt, or alternatively,they can extend at angles between 0 and 90 degrees relative to the upperand lower edges of the skirt, as described above.

The inner skirt 16 can be sutured to the frame 12 at locations away fromthe suture line 154 so that the skirt can be more pliable in that area(see FIG. 28, where the suture line follows the marking suture 136, asdiscussed below). This configuration can avoid stress concentrations atthe suture line 154, which attaches the lower edges of the leaflets tothe skirt 16.

As noted above, the leaflet structure 14 in the illustrated embodimentincludes three flexible leaflets 40 (although a greater or a smallernumber of leaflets can be used). As best shown in FIG. 21, each leaflet40 in the illustrated configuration has an upper (outflow) free edge 110extending between opposing upper tabs 112 on opposite sides of theleaflet. Below each upper tab 112 there is a notch 114 separating theupper tab from a corresponding lower tab 116. The lower (inflow) edgeportion 108 of the leaflet extending between respective ends of thelower tabs 116 includes vertical, or axial, edge portions 118 onopposites of the leaflets extending downwardly from corresponding lowertabs 116 and a substantially V-shaped, intermediate edge portion 120having a smooth, curved apex portion 119 at the lower end of the leafletand a pair of oblique portions 121 that extend between the axial edgeportions and the apex portion. The oblique portions can have a greaterradius of curvature than the apex portion. Each leaflet 40 can have areinforcing strip 72 secured (e.g., sewn) to the inner surface of thelower edge portion 108, as shown in FIG. 22.

The leaflets 40 can be secured to one another at their adjacent sides toform commissures 122 of the leaflet structure. A plurality of flexibleconnectors 124 (one of which is shown in FIG. 23) can be used tointerconnect pairs of adjacent sides of the leaflets and to mount theleaflets to the commissure window frame portions 30. The flexibleconnectors 124 can be made from a piece of woven PET fabric, althoughother synthetic and/or natural materials can be used. Each flexibleconnector 124 can include a wedge 126 extending from the lower edge tothe upper edge at the center of the connector. The wedge 126 cancomprise a non-metallic material, such as a rope, a braided yarn, or amonofilament yarn, for example, Ethibond Excel® 2-0 suture material(Johnson & Johnson, New Brunswick, N.J.), secured to the connector witha temporary suture 128. The wedge 126 helps prevent rotational movementof the leaflet tabs once they are secured to the commissure window frameportions 30. The connector 124 can have a series of inner notches 130and outer notches 132 formed along its upper and lower edges.

FIG. 24 shows the adjacent sides of two leaflets 40 interconnected by aflexible connector 124. The opposite end portions of the flexibleconnector 124 can be placed in an overlapping relationship with thelower tabs 116 with the inner notches 130 aligned with the verticaledges of the tabs 116. Each tab 116 can be secured to a correspondingend portion of the flexible connector 124 by suturing along a lineextending from an outer notch 132 on the lower edge to an outer notch132 on the upper edge of the connector. Three leaflets 40 can be securedto each other side-to-side using three flexible connectors 124, as shownin FIG. 25.

Referring now to FIGS. 26 and 27, the adjacent sub-commissure portions118 of two leaflets can be sutured directly to each other. In theexample shown, PTFE 6-0 suture material is used to form in-and-outstitches and comb stitches 133, 134 that extend through thesub-commissure portions 118 and the reinforcing strips 72 on bothleaflets. The two remaining pairs of adjacent sub-commissure portions118 can be sutured together in the same manner to form the assembledleaflet structure 14, which can then be secured to the frame 12 in thefollowing manner.

As noted above, the inner skirt 16 can be used to assist in suturing theleaflet structure 14 to the frame. As shown in FIG. 28, the skirt 16 canhave an undulating temporary marking suture 136 to guide the attachmentof the lower edges of each leaflet 40. The skirt 16 itself can besutured to the struts of the frame 12 using sutures 70, as noted above,before securing the leaflet structure 14 to the skirt 16. The strutsthat intersect the marking suture 136 desirably are not attached to theskirt 16. This allows the skirt 16 to be more pliable in the areas notsecured to the frame and minimizes stress concentrations along thesuture line that secures the lower edges of the leaflets to the skirt.The portion of the skirt 16 demarcated by rectangle 140 initially isleft unsecured to the frame 12, and is later secured to the frame afterthe leaflet structure 14 is secured to the skirt, as further describedbelow. As noted above, when the skirt is secured to the frame, thefibers 78, 80 of the skirt (see FIG. 16B) generally align with theangled struts of the frame to promote uniform crimping and expansion ofthe frame.

FIG. 29 is a cross-sectional view of a portion of the frame and leafletstructure showing the adjacent tab portions of two leaflets secured to acorresponding window frame portion 30. FIGS. 30-36 show one specificapproach for securing the commissure portions 122 of the leafletstructure 14 to the commissure window frame portions 30 of the frame.First, as shown in FIG. 30, the flexible connector 124 securing twoadjacent sides of two leaflets is folded widthwise and the upper tabportions 112 are folded downwardly against the flexible connector. Asbest shown in FIGS. 30 and 31, each upper tab portion 112 is creasedlengthwise (vertically) to assume an L-shape having an inner portion 142folded against the inner surface of the leaflet and an outer portion 144folded against the connector 124. The outer portion 144 can then besutured to the connector 124 along a suture line 146. Next, as shown inFIG. 31, the commissure tab assembly (comprised of a pair of lower tabportions 116 connected by connector 124) is inserted through thecommissure window 20 of a corresponding window frame portion 30. FIG. 32is a side view of the frame 12 showing the commissure tab assemblyextending outwardly through the window frame portion 30.

As best shown in FIGS. 29 and 33, the commissure tab assembly is pressedradially inwardly at the wedge 126 such that one of the lower tabportions 116 and a portion of the connector 124 is folded against theframe 12 on one side of the window frame portion 30 and the other lowertab portion 116 and a portion of the connector 124 is folded against theframe 12 on other side of the window frame portion 30. A pair of suturelines 148 is formed to retain the lower tab portions 116 against theframe 12 in the manner shown in FIG. 29. Each suture line 148 extendsthrough connector 124, a lower tab portion 116, the wedge 126, andanother portion of connector 124. Then, as shown in FIGS. 29 and 34,each lower tab portion 116 is secured to a corresponding upper tabportion 112 with a primary suture line 150 that extends through onelayer of connector 124, the lower tab portion 116, another layer ofconnector 124, another layer of connector 124, and the upper tab portion112. Finally, as shown in FIGS. 29 and 35, the suture material used toform the primary suture line 150 can be used to further form whipstitches 152 at the edges of the tab portions 112, 116 that extendthrough two layers of connector 124 sandwiched between tab portions 112,116.

As shown in FIGS. 29 and 30, the folded down upper tab portions 112 forma double layer of leaflet material at the commissures. The innerportions 142 of the upper tab portions 112 are positioned flat, abuttinglayers of the two leaflets 40 forming the commissures, such that eachcommissure comprises four layers of leaflet material just inside of thewindow frames 30. This four-layered portion of the commissures can bemore resistant to bending, or articulating, than the portion of theleaflets 40 just radially inward from the relatively more-rigidfour-layered portion. This causes the leaflets 40 to articulateprimarily at inner edges 143 of the folded-down inner portions 142 inresponse to blood flowing through the prosthetic valve during operationwithin the body, as opposed to articulating about or proximal to theaxial struts of the window frames 30. Because the leaflets articulate ata location spaced radially inwardly from the window frames 30, theleaflets can avoid contact with and damage from the frame. However,under high forces, the four layered portion of the commissures can splayapart about a longitudinal axis 145 (FIG. 29) adjacent to the windowframe 30, with each inner portion 142 folding out against the respectiveouter portion 144. For example, this can occur when the prosthetic valve10 is compressed and mounted onto a delivery shaft, allowing for asmaller crimped diameter. The four-layered portion of the commissurescan also splay apart about axis 145 when the balloon catheter isinflated during expansion of the prosthetic valve, which can relievesome of the pressure on the commissures caused by the balloon, reducingpotential damage to the commissures during expansion.

After all three commissure tab assemblies are secured to respectivewindow frame portions 30, the lower edges of the leaflets 40 between thecommissure tab assemblies can be sutured to the inner skirt 16. Forexample, as shown in FIGS. 36-38, each leaflet 40 can be sutured to theskirt 16 along suture line 154 using, for example, Ethibond Excel® PETthread. The sutures can be in-and-out sutures extending through eachleaflet 40, the skirt 16, and each reinforcing strip 72. Each leaflet 40and respective reinforcing strip 72 can be sewn separately to the skirt16. In this manner, the lower edges of the leaflets are secured to theframe 12 via the skirt 16. As shown in FIG. 38, the leaflets can befurther secured to the skirt with blanket sutures 156 that extendthrough each reinforcing strip 72, leaflet 40 and the skirt 16 whilelooping around the edges of the reinforcing strips 72 and leaflets 40.The blanket sutures 156 can be formed from PTFE suture material. FIGS.39 and 40 show two rotated side views of the frame 12, leaflet structure14 and the skirt 16 after securing the leaflet structure and the skirtto the frame and the leaflet structure to the skirt.

FIG. 41 shows a flattened view of the outer skirt 18 prior to itsattachment to the frame 12. The outer skirt 18 can be laser cut orotherwise formed from a strong, durable piece of material. The outerskirt 18 can have a substantially straight lower edge 160 and an upperedge 162 defining a plurality of alternating projections 164 and notches166, or castellations. As best shown in FIG. 42, the lower edge 160 ofthe skirt 18 can be sutured to the lower edge of the inner skirt 16 atthe inflow end of the prosthetic valve. As shown in FIG. 43, eachprojection 164 can be sutured to the second rung II of struts 24 of theframe 12. The upper edges 162 of the projections 164 can be folded overrespective struts of rung II and secured with sutures 168.

As can be seen in FIGS. 1-3 and 42-43, the outer skirt 18 is secured tothe frame 12 such that when the frame is in its expanded configuration(e.g., when deployed in a subject), there is excess material between thelower edge 160 and the upper edge 162 that does not lie flat against theouter surface of the frame 12. The outer skirt 18 can be secureddirectly to frame 12 and/or indirectly to frame 12, for example, bysecuring the outer skirt to the inner skirt, which is directly securedto the frame 12. In the expanded configuration of the prosthetic valve,the distance between the upper and lower attachment points of the outerskirt 18 decreases (foreshortens), resulting in outward radial bucklingof the outer skirt 18. Additionally, the excess material between thelower and upper edges of the outer skirt 18 allows the frame 12 toelongate axially when crimped without any resistance from the outerskirt. In some embodiments, the skirt 18 includes an axial length orheight that can be substantially the same as the axial length betweenthe upper and lower attachment points of the skirt 18 to the frame 12when the frame is fully crimped. In such embodiments, when the frame 12is fully crimped, the outer skirt can lie flat against the outer surfaceof the frame 12.

In some embodiments, the outer skirt 18 can comprise a fabric 170 thatis stiffer in the axial direction 172 than it is in the circumferentialdirection 173 when mounted on frame 12 in order to enhance outwardradial buckling or expansion of the outer skirt 18 (see FIG. 44). Forexample, the fabric 170 can be woven from a first set of fibers (oryarns or strands) 176, and a second set of fibers (or yarns or strands)178. The fabric 170 can include a weave of warp fibers comprising thefirst set of fibers 176 and weft fibers comprising the second set offibers 178. Alternatively, the fabric 170 can include a weave of warpfibers comprising the second set of fibers 178 and weft fiberscomprising the first set of fibers 176.

The first set of fibers 176 can comprise monofilaments that are stifferthan the fibers in the second set of fibers 178. Examples of suitablemonofilaments include, but are not limited to, those made of polymer ormetal wires, such as PET, PTFE, and/or NiTi. In some embodiments, themonofilament can have a diameter of from about 0.05 mm to about 0.5 mm(about 0.002-0.02 inches). The second set of fibers 178 can comprisemultifilaments and/or microfibers that are less stiff than the fibers inthe first set of fibers 176. Examples of suitable multifilaments and/ormicrofibers include, but are not limited to, those made of polymer, suchas PET and/or PTFE. In some embodiments, the second set of fibers 178can comprise a mixture of materials (such as a mixture of multifilamentsand microfibers) that has an overall stiffness that is less than thefirst set of fibers 176.

The fibers in the first or second sets of fibers do not need to be thesame types of fibers, for example, the first set of fibers can includemonofilaments, microfilaments, and/or microfibers, as long as the fabric170 is stiffer in the axial direction than the circumferential directionwhen mounted on prosthetic valve 10. Likewise, the second set of fiberscan include monofilaments, microfilaments, and/or microfibers.

In some embodiments, the fabric 170 comprises more parallel fibers perunit length in the axial direction than fibers per unit length in thecircumferential direction. Thus, the fabric 170 includes an increaseddensity of fibers running in the axial direction compared to fibersrunning in the circumferential direction.

In additional embodiments, the outer skirt 18 can comprise aself-expandable fabric 230 that comprises one or more fibers made of ashape-memory material, such as NiTi (see FIG. 57). For example, the oneor more fibers made of a shape-memory material can be included in theweave of the self-expandable fabric 230, or can be otherwise secured toattached (for example, by suture) to a fabric to make theself-expandable fabric 230. The shape memory of such fibers can be setto enhance the radial outward buckling or expansion of the outer skirt18 when it is mounted on the frame 12. Additionally, the fibers of shapememory material in the self-expandable fabric 230 can be comprisedifferent shape memories as needed to conform to particular anatomicalstructures. Thus, the self-expandable fabric 230 can be woven orconstructed to have a plurality of fibers made of shape memory materialwith a shape memory set such that the fabric comprises athree-dimensional shape that conforms to particular anatomical structurein a patient.

When constructed of the self-expandable fabric 230, the outer skirt canbe crimped to a radially collapsed configuration and restrained in thecollapsed configuration by insertion of the prosthetic valve includingthe outer skirt into a sheath or equivalent mechanism of a deliverycatheter. Once inside the body, the prosthetic valve can be advancedfrom the delivery sheath, which allows the prosthetic valve and theouter skirt to expand to their functional size.

With reference to FIG. 57, the self-expandable fabric 230 can be wovenfrom a first set of fibers (or yarns or strands) 232, and a second setof fibers (or yarns or strands) 234. The self-expanding fabric 230 canbe positioned on the frame 12 in any orientation that facilitates theradial outward buckling or expansion of the outer skirt 18. For example,as shown in FIG. 57, the self-expandable fabric 230 of the outer skirt18 can include a weave of warp fibers in an axial direction 236comprising the first set of fibers 232 and weft fibers in acircumferential direction 238 comprising the second set of fibers 234.In another embodiment, the self-expandable fabric 230 of the outer skirt18 can include a weave of weft fibers in the axial direction 236comprising the first set of fibers 232 and warp fibers in thecircumferential direction 238 comprising the second set of fibers 234.

The first set of fibers 232 comprises one or more fibers that are madeof a shape-memory material comprising a shape memory set to enhance theradially outward buckling of the outer skirt 18. For example, the fiberscan be NiTi wires that have sufficient elongation to withstand weavingstress and a sufficiently large diameter to self-load and push adjacentfibers towards the set shape of the nitinol wire.

In several embodiments, such NiTi wires can comprise a diameter of from0.5-15 Mils, such as from 4-6 Mils, from 1-5 Mils, from 2-5 Mils, from3-5 Mils, from 4-7 Mils, or from 4-6 Mils in diameter. For example, insome embodiments, the NiTi wires can comprise a diameter of from 0.002to 0.005 inches, such as about 0.002, about 0.003, about 0.004, or about0.005 inches in diameter. The shape memory of any NiTi wires in theself-expandable fabric 230 can be set to a shape that will enhance theradial outward buckling of the outer skirt 18 before being woven intothe fabric. In one example, the shape memory of the NiTi wires can betrained by heating to greater than 500° C. for 2 hours followed by agingat 450° C. for 90 minutes. The heating can be performed in an air orvacuum furnace followed by rapid (preferably water) quenching. After theshape memory of the NiTi wire is set, the wire can be woven into theself-expandable fabric 230. In some embodiments, 5-25 percent (such as5-10, 5-15, 5-20, 10-15, 10-20, 10-25, 15-20, 15-25, or 20-25 percent)of the weft fibers in the self-expandable fabric of the outer skirt 18can be made of the shape-memory material. In some embodiments, up to100% of the weft fibers in the self-expandable fabric of the outer skirt18 can be made of the shape-memory material.

In certain embodiments, the first set of fibers 232 (including the NiTiwires) are the weft fibers of the weave. In alternative embodiments, thefirst set of fibers 232 (including the NiTi wires) are the warp fibersof the weave. The remaining fibers in the first and second sets offibers can also be made of a shape memory material (such as NiTi)comprising a shape memory set to enhance the radially outward bucklingof outer skirt 18. Alternatively, the remaining fibers can be made of anon-shape-memory material, such as PET or PTFE. The remaining fibers donot need to be the same types of fibers, for example, the first and/orsecond set of fibers can include monofilaments, microfilaments, and/ormicrofibers. Examples of suitable monofilaments, microfilaments, and/ormicrofibers include, but are not limited to, those made of polymer suchas PET or PTFE. In some embodiments, the monofilament or microfiber canhave a diameter of from about 0.05 mm to about 0.5 mm (about 0.002-0.02inches).

As noted above, the fabric 230 can be positioned on the frame 12 in anyorientation that facilitates outward buckling and expansion of the outerskirt. In some implementations, the outer skirt 18 has shape memoryfibers (e.g., NiTi wires) only in the axial direction. In otherimplementations, the outer skirt 18 has shape memory fibers (e.g., NiTiwires) only in the circumferential direction. In still otherimplementations, the outer skirt 18 has shape memory fibers (e.g., NiTiwires) in the axial and circumferential directions.

As shown in FIG. 57, the warp and weft fibers in the self-expandablefabric 230 can be in a plain weave. Alternative weave patterns can alsobe utilized. For example, the self-expandable fabric 230 can comprise ahybrid weave of non-shape memory warp and weft fibers (such as PETfibers) in a plain weave pattern alternating with shape-memory weftfibers and non-shape-memory warp fibers, or shape-memory warp fibers andnon-shape-memory weft fibers, in a satin weave pattern (see FIGS.58-60). In a satin weave pattern, the float length of the weft fibers islonger than in a plain weave pattern. Thus, when the shape memory fibersare used as weft fibers in a satin weave pattern, the outward bucklingof the fabric can be increased due to fewer contact points whichprovides more freedom to the shape memory fibers to buckle outwards.Accordingly, the combination of the plain weave of non-shape-memoryfibers with the satin weave of shape-memory and non-shape memory fibersprovides an outer skirt material with superior radial outward bucklingforce.

FIGS. 58-60 show weaving diagrams illustrating three exemplary designsfor the weave of the self-expandable fabric 230. In the weaving diagramsshown in FIGS. 58-60, warp fibers are represented by columns and weftfibers are represented by rows. A square in the diagram represents theintersection of a warp fiber and a weft fiber. If the weft fiber isradially outward of the warp fiber at a particular intersection, thenthe square is marked with diagonal hatch (for shape memory fibers) orcross hatch (for non-shape memory fibers). If the warp fiber is radiallyoutward of the weft fiber (that is, the warp fiber “floats” over theweft fiber) at a particular intersection, then the square is left blank.In the illustrated weaving diagrams, the weft fibers include the shapememory fibers. However, in other embodiments, the fibers can be reversedsuch that the weft fibers are the warp fibers and the warp fibers arethe weft fibers and still provide the same weave pattern.

As illustrated in FIGS. 58-60, the rows of weft fibers in the weave canalternate between shape-memory fibers and non-shape memory fibers invarious patterns. For example, one or more rows of shape-memory weftfibers can be separated by one or more (such as 2, 3, 4, or 5, or more)rows of non-shape-memory fibers. Additionally, the number of adjacentwarp fibers that “float” over the shape-memory fiber in a particular rowcan also vary, for example from 1-2 adjacent warp fibers (e.g., as shownin FIG. 59), or 1-5 adjacent warp fibers, to up to 10 adjacent warpfibers (such as 2 adjacent warp fibers, 3 adjacent warp fibers, 4adjacent ward fibers, 5 adjacent warp fibers (as shown in FIG. 58), 6adjacent warp fibers, 7 adjacent warp fibers, 8 adjacent warp fibers (asshown in FIG. 60), or 9 adjacent warp fibers).

In some embodiments, the outer skirt 18 can comprise a self-expandablefabric 230 comprising a combination of plain and satin weave patternswith two rows of a plain weave of non-shape memory warp and weft fibersalternating with one row of a satin weave of a shape memory weft fiberand non-shape memory warp fibers. The satin weave can comprise a floatof five adjacent warp fibers between radial outward exposure of theshape memory weft fiber over a single warp fiber (see FIG. 58).

In some embodiments, the outer skirt 18 can comprise a self-expandablefabric 230 comprising a combination of plain and satin weave patternswith four rows of a plain weave of non-shape memory warp and weft fibersalternating with one row of a satin weave of a shape memory weft fiberand non-shape memory warp fibers. The satin weave can comprise a floatof one to adjacent two warp fibers between radial outward exposure ofthe shape memory weft fiber over one to two adjacent warp fibers (seeFIG. 59).

In some embodiments, the outer skirt 18 can comprise a self-expandablefabric 230 comprising a combination of plain and satin weave patternswith one row of a plain weave of non-shape memory warp and weft fibersalternating with one row of a satin weave of a shape memory weft fiberand non-shape memory warp fibers. The satin weave can comprise a floatof eight warp fibers between radial outward exposure of the shape memoryweft fiber over a single warp fiber (see FIG. 60).

As shown in FIG. 48, in the collapsed configuration, the excess materialof the outer skirt 18 forms a plurality of folds 179 extending in theaxial direction. In this configuration, the first set of fibers 176 or232 can extend axially in a substantially straight, non-foldedconfiguration, and the second set of fibers 178 or 234 include theplurality of folds 179. In several embodiments, the elastic range of thesecond set of fibers is not exceeded when the prosthetic valve 10 is inthe collapsed configuration and the outer skirt 18 forms the pluralityof folds 179. Thus, when the prosthetic valve 10 is radially expandedfrom the collapsed configuration, there is no residual strain in thesecond set of fibers (i.e., there are no wrinkles formed in the secondset of fibers). In several embodiments, the second set of fibers 178 or234 comprises a set of multifilaments and/or microfibers each having anindividual diameter that is small enough such that the elastic range ofthe multifilaments and/or microfibers is not exceeded when theprosthetic valve 10 is in the collapsed configuration and the outerskirt 18 comprises the plurality of folds 179. In such embodiments,there is no residual strain on the second set of fibers 178 or 234 afterthe prosthetic valve 10 has been compressed to the collapsedconfiguration. Thus, in several embodiments, the second set of fibers178 or 234 comprises or consists of fibers that are “wrinkle-free,” thatis, the second set of fibers 178 or 234 does not exceed its elasticrange and does not comprise residual strain (i.e., wrinkles) after theprosthetic valve 10 is compressed to its fully collapsed configurationand has formed the plurality of folds 179 in the outer skirt 18.

When the prosthetic valve 10 is deployed within the body, the excessmaterial of an intermediate portion of the outer skirt 18 that bucklesoutwardly can fill in gaps between the frame 12 and the surroundingnative annulus to assist in forming a good, fluid-tight seal between theprosthetic valve and the native annulus. The outer skirt 18 thereforecooperates with the inner skirt 16 to avoid perivalvular leakage afterimplantation of the prosthetic valve 10. In several embodiments, theprosthetic valve 10 comprising the outer skirt 18 that buckles outwardlycan have reduced perivalvular leakage when implanted in a subjectcompared to a similar prosthetic valve that lacks the outer skirt 18.

FIG. 48 shows the prosthetic valve 10 of FIGS. 1-3 and 42-43 mounted onan elongated shaft 180 of a delivery apparatus, forming a deliveryassembly for implanting the prosthetic valve 10 in a patient's body. Theprosthetic valve 10 is mounted in a radially collapsed configuration fordelivery into the body. The shaft 180 comprises an inflatable balloon182 for expanding the prosthetic valve within the body, the crimpedprosthetic valve 10 being positioned over the deflated balloon. Theframe 12 of the prosthetic valve 10, when in the radially compressed,mounted configuration, can comprise an inflow end portion 174 (see FIG.46) that has an outer diameter D₂ that is smaller than the outerdiameter D₁ of the outflow end portion of the frame. The tapering of theframe can be at least partially due to the V-shaped leaflets 40, as theV-shaped leaflets have less leaflet material within the inflow endportion of the frame 12 compared to a more rounded, U-shaped leaflet.Due to the tapered shape of the frame 12 in the mounted configuration,even with the additional thickness of the outer skirt 18 positionedaround the inflow end portion 174 of the frame 12, the overall outerdiameter of the inflow end portion of the prosthetic valve 10 can beabout equal to, or less than, the overall outer diameter of the outflowend portion of the prosthetic valve.

Furthermore, as shown in FIG. 48, the prosthetic valve 10 can comprisecommissure portions of the leaflets extending radially outwardly throughcorresponding window frame portions 30 to locations outside of the frameand sutured to the side struts of the commissure window frame. Tominimize the crimp profile of the prosthetic valve, the window frameportions 30 can be depressed radially inwardly relative to thesurrounding portions of the frame, such as the frame portions extendingbetween adjacent commissure windows, when the prosthetic valve isradially compressed to the collapsed configuration on the shaft. Forexample, the commissure windows 30 of the frame can be depressedinwardly a radial distance of between from about 0.2 mm to about 1.0 mmrelative to the portions of the frame extending between adjacentcommissure windows when the prosthetic valve is radially collapsed. Inthis way, the outer diameter of the outflow end portion the prostheticvalve comprising the commissure portions can be generally consistent, asopposed to the commissure portions jutting outwardly from thesurrounding portions of the prosthetic valve, which could hinderdelivery of the prosthetic valve into the body. Even with the radiallydepressed commissure window frames 30, the outer diameter of the inflowend of the frame can still be smaller than, or about equal to, the outerdiameter of the outflow end of the frame when the prosthetic valve isradially collapsed on the shaft, allowing for a minimal maximum overalldiameter of the prosthetic valve. By minimizing the diameter of theprosthetic valve when mounted on the delivery shaft, the assembly cancontained within a smaller diameter catheter and thus can be passedthrough smaller vessels in the body and can be less invasive in general.

FIGS. 49-51 illustrate expansion of an embodiment of the prostheticvalve 10 from a radially collapsed configuration as shown in FIG. 49 toa radially expanded state as shown in FIG. 51. The prosthetic valve 10is mounted on a balloon 182 of a delivery shaft 180, and comprises theinflow end portion 15, the outflow end portion 19 and the intermediateportion 17. For clarity, the outer skirt 18 and frame 12 of theprosthetic valve 10 is shown, but other components of the prostheticvalve, such as the leaflets and the inner skirt, are not shown. Theframe 12 can have a reduced thickness at the inflow end portion 15 andat the outflow end portion 19, relative to the thickness of theintermediate portion 17. Due to the thinner end portions, when theballoon 182 is inflated the end portions 15 and 19 offer less resistanceto expansion and expand faster than the intermediate portion 17, asshown in FIG. 50. Because the end portions expand faster than theintermediate portion, the frame 12 becomes confined on the balloon 182,inhibiting the frame from sliding towards either end of the balloon andreducing the risk of the frame sliding off the balloon prematurely. Asshown in FIG. 51, further inflation of the balloon can cause theintermediate portion 17 of the frame to expand to the same finaldiameter as the end portions 15 and 19 for implantation, after which theballoon can be deflated and removed. Controlling the position of theprosthetic valve on the balloon can be important during delivery,especially with frames that foreshorten during expansion and moverelative to the balloon. In the embodiment shown in FIGS. 49-51, theintermediate portion 17 of the frame can be held constant relative tothe balloon while the two end portions foreshorten towards theintermediate portion due to the “dog-bone” effect of the balloon. Anysuitable means can be used to produce the frame 12 with reducedthickness at the end portions 15 and 19, such as contacting the endportions with abrasive, drawing portions of a hypotube prior to lasercutting, laser ablation, water-jet machining, machining, or the like. Inone embodiment, the end portions 15 and 19 of the frame have a thicknessof about 0.37 mm while the intermediate portion 17 has a thickness ofabout 0.45 mm.

Although described in the context of prosthetic valve 10, the outerskirt 18 comprising the fabric 170 that is stiffer in the axialdirection than in the circumferential direction, or the self-expandablefabric 230 comprising fibers made of shape memory material can beincluded as an outer skirt on any suitable prosthetic valve, such as anysuitable prosthetic heart valve, known in the art. In severalembodiments, the outer skirt 18 comprising the fabric 170 that isstiffer in the axial direction than the circumferential direction or theself-expandable fabric 230 comprising fibers made of shape memorymaterial can be included in place of an outer skirt on a knownprosthetic heart valve. Non-limiting examples of suitable prostheticheart valves for which that outer skirt 18 comprising the fabric 170that is stiffer in the axial direction than the circumferentialdirection or the self-expandable fabric 230 comprising fibers made ofshape memory material include those disclosed in U.S. and InternationalPatent Publication Nos. US2012/0123529, WO2011/126758, WO2012/048035,WO2014/004822, WO2010/022138A2, U.S. Pat. Nos. 8,591,570, and 8,613,765,each of which is incorporated by reference herein in its entirety.

Further, although described in the context of the outer skirt 18 of theprosthetic valve 10, the self-expandable fabric 230 comprising fibersmade of shape memory material can also be used in sheet form as ascaffold for tissue engineering with shape memory effect customized toparticular anatomical shapes.

The prosthetic valve 10 can be configured for and mounted on a suitabledelivery apparatus for implantation in a subject. Several catheter-baseddelivery apparatuses are known; a non-limiting example of a suitablecatheter-based delivery apparatus includes that disclosed in U.S. PatentApplication Publication Nos. US2012/0123529 and US2013/0030519, whichare incorporated by reference herein in its entirety.

The prosthetic valve, once assembled, can be treated with any one of acombination of various chemical agents that can help to preventrejection of the prosthetic valve by the recipient, to sterilize theprosthetic valve, to stabilize proteins in the prosthetic valve leaflettissue, to make the tissue more resistant to mechanical fatigue, toreduce degradation of the tissue by proteolytic enzymes, and/or to allowpackaging or delivery of the prosthetic valve in a dry form. Inalternative embodiments, the leaflets of the prosthetic valve can betreated with chemical agents prior to being secured to the frame.

Some prosthetic heart valves are typically packaged in jars filled withpreserving solution for shipping and storage prior to implantation intoa patient, though techniques are also known for drying and storingbioprosthetic heart valves without immersing them in a preservativesolution. The term “dried” or “dry” bioprosthetic heart valves referssimply to the ability to store those bioprosthetic heart valves withoutthe preservative solutions, and the term “dry” should not be consideredsynonymous with brittle or rigid. Indeed, “dry” bioprosthetic heartvalve leaflets may be relatively supple even prior to implant. There area number of proposed methods for drying bioprosthetic heart valves, andfor drying tissue implants in general, and the present applicationcontemplates the use of bioprosthetic heart valves processed by any ofthese methods. A particularly preferred method of drying bioprostheticheart valves is disclosed in U.S. Pat. No. 8,007,992 to Tian, et al. Analternative drying method is disclosed in U.S. Pat. No. 6,534,004 toChen, et al. Again, these and other methods for drying bioprostheticheart valves may be used prior to using the crimping systems and methodsdescribed herein.

One such strategy is to dehydrate the bioprosthetic tissue in aglycerol/ethanol mixture, to sterilize with ethylene oxide, and topackage the final product “dry.” This process eliminates the potentialtoxicity and calcification effects of glutaraldehyde as a sterilant andstorage solution. There have been several methods proposed that usesugar alcohols (e.g., glycerol), alcohols, and combinations thereof inpost-glutaraldehyde processing methods so that the resulting tissue isin a “dry” state rather than a wet state in which the tissue is storedin a solution comprising excess glutaraldehyde. U.S. Pat. No. 6,534,004(Chen et al.) describes the storage of bioprosthetic tissue inpolyhydric alcohols such as glycerol. In processes where the tissue isdehydrated in an ethanol/glycerol solution, the tissue may be sterilizedusing ethylene oxide (ETO), gamma irradiation, or electron beamirradiation.

More recently, Dove, et al. in U.S. Patent Application Publication No.2009/0164005 propose solutions for certain detrimental changes withindehydrated tissue that can occur as a result of oxidation. Dove, et al.propose permanent capping of the aldehyde groups in the tissue (e.g., byreductive amination). Dove, et al. also describe the addition ofchemicals (e.g., antioxidants) to the dehydration solution (e.g.,ethanol/glycerol) to prevent oxidation of the tissue duringsterilization (e.g., ethylene oxide, gamma irradiation, electron beamirradiation, etc.) and storage. Tissue processed in accordance with theprinciples disclosed in Dove, et al. are termed, “capped tissue”, andtherefore bioprosthetic heart valves which use such tissue are termed,“capped tissue valves”. Capping the glutaraldehyde terminates thecross-linking process by consuming all or nearly all of the freealdehyde groups, and it is believed that this in conjunction withremoving the prosthetic tissue valve from the cross-linking solution(e.g., glutaraldehyde) by storing dry is the most effective way toterminate the cross-linking process.

Once treated with appropriate chemical agents, the prosthetic valve canbe crimped to a small profile, suited for implantation in a recipientand/or delivery to a health care provider. The prosthetic valve can becrimped directly onto a delivery device (e.g., on the balloon of aballoon catheter or on a shaft of a balloon catheter adjacent to theballoon). Once crimped, the prosthetic valve can be packaged in asterile package in a dry state along with the delivery catheter (or justportion of the delivery catheter) on which the prosthetic valve ismounted and then delivered to a healthcare facility. The prostheticvalve and the delivery catheter can be stored until it is needed for aprocedure, at which point the physician can remove the prosthetic valveand the delivery catheter from the package and then implant theprosthetic valve in a patient.

FIG. 52 illustrates a multi-step process 200 for crimping an expandableand collapsible prosthetic valve (such as a valve 12) comprising anoutflow end portion and an inflow end portion, and an outer skirt (suchas an outer skirt 18) on the inflow end portion. The outer skirt has anupper edge and a lower edge that are connected to the prosthetic valve,as described for outer skirt 18 above. By using the multi-step process200, the prosthetic valve including an outer skirt (such as outer skirt18) can be crimped to a small diameter without uneven buckling orcrushing of the outer skirt. Using the multi-step process 200, theprosthetic valve can be crimped to a small profile, suited forimplantation in a recipient. Alternatively, the prosthetic valve can becrimped to partially collapsed profile for delivery to a health careprovider for further crimping prior to implantation in a recipient. Theprosthetic valve can be crimped directly onto a delivery device (e.g.,onto the balloon of a balloon catheter or onto a shaft of a ballooncatheter adjacent the balloon). Once crimped (partially or fully), theprosthetic valve can be packaged in a sterile package alone or alongwith the delivery catheter and then delivered to a health care provider.The prosthetic valve and the delivery catheter can be stored untilneeded for a procedure, at which point the physician can remove theprosthetic valve and the delivery catheter from the package and thenimplant the prosthetic valve in a patient. In alternative embodiments,the prosthetic valve can be provided to health care providers in a fullyexpanded state. Process 200 can be used by the end user to crimp theprosthetic valve on a delivery apparatus just prior to implantation.

As shown in FIG. 52 at process block 202, the process 200 begins byreceiving an expandable prosthetic valve in a fully expandedconfiguration. The crimping process can continue by partially insertingthe expanded prosthetic valve into a valve crimper, at process block204. The outflow end portion of the prosthetic valve can be insertedinto the crimping device in a position where the jaws of the crimpingdevice can contact the frame of the prosthetic valve. The portion of theprosthetic valve covered with the outer skirt is located outside thecrimping aperture of the crimping device such that the crimper jaws(when actuated) do not contact the outer skirt, or, alternatively,contact the upper edge or portion of the outer skirt (such as the upperedge of outer skirt 18 or the plurality of alternating projections 164and notches 166 of outer skirt 18), but do not contact the intermediateportion of the outer skirt.

At process block 206, the prosthetic valve is crimped to a firstpartially collapsed configuration. As discussed above for outer skirt18, when the collapsible and expandable prosthetic valve is crimped tothe fully collapsed configuration, the distance between the upper andlower attachment point of the outer skirt elongates, resulting inflattening of the outer skirt against the frame of the prosthetic valve.Thus, when the prosthetic valve is crimped to the first partiallycollapsed configuration at process block 206, the distance between theupper and lower attachment point of the outer skirt elongates resultingin partial flattening of the outer skirt against the frame of theprosthetic valve. This partial flattening is due to the elongation forthe frame of the prosthetic valve in the axial direction. Due to thepartial flattening, axially extending folds form in the outer skirt.Although the prosthetic valve is not fully inserted into the crimper,radial compression of the portion of the prosthetic valve that isinserted between the crimper jaws results in a corresponding radialcollapse of the portion of the prosthetic valve that is not insertedbetween the crimper jaws during this crimping step.

In some embodiments, an expandable prosthetic valve can be consideredcrimped to the first partially collapsed configuration and process block206 can accordingly be considered complete when the distance between theupper and lower attachment point of the outer skirt is elongated toabout 20%, about 30%, about 40%, about 50%, or about 60% (such asbetween about 20% and about 60%) of the distance between the upper andlower attachment point of the outer skirt in the fully collapsedconfiguration, resulting in partial flattening of the outer skirtagainst the frame of the prosthetic valve. In other embodiments, anexpandable prosthetic valve can be considered crimped to the firstpartially collapsed configuration and process block 206 can accordinglybe considered complete when the prosthetic valve has a diameter that isabout 60% or about 50% (such as between about 40% and about 60%) of thediameter of the prosthetic valve in the fully expanded configuration. Inmore embodiments, an expandable prosthetic valve can be consideredcrimped to the first partially collapsed configuration and process block206 can accordingly be considered complete when the valve outsidediameter is be from about 15-20 mm at the outflow side, and from about15-26 mm at the inflow side. The difference in outer diameter betweenthe inflow and outflow sides of the valve is due to the outer skirt,which can add from about 1-5 mm to the outside diameter of the inflowend portion.

At process block 208, the prosthetic valve is fully inserted into thecrimping jaws.

The crimping process can continue at process block 210 by crimping theexpandable prosthetic valve to a second partially collapsedconfiguration. In some embodiments, the expandable prosthetic valve canbe considered crimped to the second partially collapsed configurationand process block 210 can accordingly be considered complete when thedistance between the upper and lower attachment point of the outer skirtis elongated to about 70%, about 80%, or about 90% (such as at leastabout 70%) of the distance between the upper and lower attachment pointsof the outer skirt in the fully collapsed configuration, resulting inadditional flattening of the outer skirt against the frame of theprosthetic valve. In other embodiments, an expandable prosthetic valvecan be considered crimped to the second partially collapsedconfiguration and process block 206 can accordingly be consideredcomplete when the prosthetic valve has a diameter that is about 40% orabout 30% (such as no more than about 40%) of the diameter of theprosthetic valve in the fully expanded configuration. The outer skirtcan add from about 1-4 mm to the outside diameter of the inflow endportion of the valve in the second partially collapsed configuration.

The crimping process can optionally continue at process block 212 bycrimping the expandable prosthetic valve to a fully collapsedconfiguration. In some embodiments, the expandable prosthetic valve canbe considered crimped to the fully collapsed configuration and processblock 212 can accordingly be considered complete when the diameter ofthe frame 12 of the prosthetic valve 10 is no more than about 5 mm. Inadditional embodiments the frame 12 of the prosthetic valve 10 has adiameter of no more than about 14 Fr in the fully crimped configuration.In one non-limiting example, the frame of a 26-mm prosthetic valve, whenfully crimped, has a diameter of no more than about 14 Fr. The outerskirt can add about 1 Fr to the outside diameter of the inflow endportion of the valve in the fully collapsed configuration.

The crimping process can continue by removing the prosthetic valve fromthe crimping device at process block 214. At the completion of any ofthe process blocks 202, 204, 206, 208, and/or 210, the process can bepaused for any appropriate period of time. That is, a succeeding processblock need not begin immediately upon termination of a preceding processblock.

In various embodiments, the prosthetic valve can be removed from thecrimping device at the completion of steps 206 or 210 and then packagedin a sterile package for storage and/or delivery to a health careprovider, with the remaining steps of the process 200 to be completed bythe end user. In particular embodiments, the crimped or partiallycrimped prosthetic valve is packaged in a dry state. In alternativeembodiments, the crimped or partially crimped prosthetic valve ispackaged in a “wet” state within a container containing a preservingsolution.

FIGS. 53-55 schematically illustrate process blocks 204-210 of themulti-step process 200 for crimping an expandable and collapsibleprosthetic valve comprising an outer skirt, in the context of crimpingthe prosthetic valve 10 comprising the outer skirt 18 using a crimpingdevice 215. The crimping device 215 can include a plurality ofcircumferentially arranged crimping jaws 216 (two of which are shown inthe drawings) that define a variable diameter crimping aperture 217. Thecrimping jaws 216 can be moved radially inwardly relative to each otherto decrease the size of the aperture 217, thereby radially compressing aprosthetic valve disposed in the aperture 217. Further details regardingthe construction of the crimping device 215 are disclosed in U.S. Pat.No. 7,530,253, which is incorporated by reference herein in itsentirety.

As shown in FIG. 53, the outflow end portion 19 of the prosthetic valve10 in a fully expanded configuration can be inserted between the crimperjaws 216 of the crimping device 215 up to the upper edge 162 of theouter skirt 18. The inflow end portion 15 of the prosthetic valve 10including the outer skirt 18 protrudes from the crimper jaws 216, suchthat the crimper jaws (when actuated to move radially inwardly) do notcontact the outer skirt 18. In an alternative embodiment (not pictured),the prosthetic valve 10 can be inserted into the crimping device 215 upto the plurality of alternating notches 166 (FIG. 41), such that thecrimper jaws 216 (when actuated) contact the plurality of alternatingprojections 164 and notches 166, but do not contact the remainder of theouter skirt 18.

As shown in FIG. 54, the crimper jaws are moved radially inwardly in thedirection of arrows 218, resulting in radial compression of theprosthetic valve 10 to the first partially collapsed configuration 222.As the prosthetic valve 10 collapses, the distance between the upper andlower attachment point of the outer skirt 18 elongates, resulting inpartial flattening of the outer skirt against the frame 12 of theprosthetic valve 10. Following crimping to the first partially collapsedconfiguration 222, the prosthetic valve 10 is fully inserted into thecrimper jaws 216 of crimping device 215 (FIG. 55).

As shown in FIG. 56, the crimper jaws are moved further radiallyinwardly in the direction of arrows 220, resulting in radial compressionof the prosthetic valve 10 to the second partially collapsedconfiguration 224. As the prosthetic valve 10 collapses, the distancebetween the upper and lower attachment point of the outer skirt 18elongates, resulting in additional flattening of the outer skirt againstthe frame 12 of the prosthetic valve 10.

The prosthetic valve 10 can be removed from the crimping devicefollowing crimping to the second partially crimped configuration 224.For example, in some embodiments, the prosthetic valve 10 can be crimpedto the second partially collapsed configuration and then removed fromthe crimping device and packaged for storage or delivery to a healthcare provider, and the prosthetic valve can be fully crimped by aphysician before implantation into a subject. In other embodiments, theprosthetic valve 10 can be further crimped to a fully collapsedconfiguration before removal from the crimping device and then packagedfor storage and/or delivery to the health care provider.

The rate at which the prosthetic valve is crimped can be adjusted asneeded for particular valves and/or crimping devices. For example, theexpandable prosthetic valve can be crimped to a first partially crimpedconfiguration at a first rate, then crimped to a second partiallycrimped configuration at a second rate, then fully crimped at a thirdrate. In another alternative embodiment, the rate at which an expandableprosthetic valve is crimped can be continuously variable and determinedbased on suitable factors such as the pressure resulting in the leafletsfrom the crimping process.

The process 200 can be used with a wide variety of prosthetic valvesthat have an outer skirt, as well as with a wide variety of crimpingdevices. The process of crimping a prosthetic valve and controlling thespeed at which a prosthetic valve is crimped can be controlled andcompleted by any of various crimping devices. For example, a prostheticvalve can be crimped manually using a manual crimping device (such asdisclosed in U.S. Pat. No. 7,530,253, incorporated by reference hereinin its entirety), or automatically using an automated crimping device(such as disclosed in U.S. patent application Ser. No. 14/211,775, filedMar. 14, 2014, which is incorporated by reference herein in itsentirety). A prosthetic valve can also be partially crimped using acrimping device (such as an automatic or manual crimping devicedisclosed in U.S. Pat. No. 7,530,253 or U.S. patent application Ser. No.14/211,775) for the first and second crimping steps, and then removedfrom the crimping device and in a further crimping step pulled through acrimping cone into a delivery sheath or a cylinder, which has an insidediameter equal to the final crimped diameter of the prosthetic valve(such as described in U.S. Patent Application Publication No.2012/0239142, which is incorporated by reference herein in itsentirety).

Appropriate crimping devices can be driven by an electric motor or acombustion engine, can be pressure regulated, or can be pneumatically orhydraulically driven. Such a system can include various devices forcollecting user input, such as buttons, levers, pedals, etc.

In view of the many possible embodiments to which the principles of thedisclosed invention may be applied, it should be recognized that theillustrated embodiments are only preferred examples of the invention andshould not be taken as limiting the scope of the invention. Rather, thescope of the invention is defined by the following claims. We thereforeclaim as our invention all that comes within the scope of these claims.

We claim:
 1. A method of radially compressing a prosthetic valve,comprising: partially inserting the valve while in a radially expandedconfiguration into a crimping device comprising crimper jaws, wherein aportion of the valve comprising an outer skirt extends outside of thecrimper jaws; crimping the valve to a first partially collapsedconfiguration; further inserting the valve into the crimping device,such that the outer skirt is between the crimper jaws; and crimping thevalve to a second partially collapsed configuration, wherein a diameterof the valve is smaller in the second partially collapsed configurationthan in the first partially collapsed configuration.
 2. The method ofclaim 1, further comprising crimping the valve to a fully collapsedconfiguration.
 3. The method of claim 2, wherein the diameter of thevalve in the fully collapsed configuration is about 10% of the diameterof the valve in the radially expanded configuration.
 4. The method ofclaim 1, wherein the diameter of the valve in the first partiallycollapsed configuration is in a range of 40% to 60% of the diameter ofthe valve in the radially expanded configuration.
 5. The method of claim1, wherein the diameter of the valve in the second partially collapsedconfiguration is no more than 40% of the diameter of the valve in theradially expanded configuration.
 6. The method of claim 1, wherein thediameter of the valve in the first partially collapsed configuration is40% to 60% of the diameter of the valve in the radially expandedconfiguration and the diameter of the valve in the second partiallycollapsed configuration is no more than 40% of the diameter of the valvein the radially expanded configuration.
 7. The method of claim 1,wherein the crimping device is an automated crimping device.
 8. Themethod of claim 1, wherein the outer skirt is positioned around an outersurface of a frame of the valve and comprises: an inflow edge secured tothe frame at a first location; an outflow edge secured to the frame at asecond location; and an intermediate portion between the inflow edge andthe outflow edge that comprises slack that buckles radially outwardsfrom the inflow and outflow edges of the outer skirt when the valve isin the radially expanded configuration.
 9. The method of claim 8,wherein the first location is an inflow end of the frame and the secondlocation is a location between the inflow end and an outflow end of theframe.
 10. The method of claim 8, wherein the outer skirt comprises afabric that is stiffer in an axial direction of the valve than acircumferential direction of the valve.
 11. The method of claim 1,wherein partially inserting the valve while in the radially expandedconfiguration into the crimping device includes inserting an outflow endportion of the valve into the crimping device and between the crimperjaws up to an outflow edge of the outer skirt that is coupled to a frameof the valve at a location between an outflow end portion and an inflowend portion of the valve.
 12. The method of claim 11, wherein furtherinserting the valve into the crimping device, such that the outer skirtis between the crimper jaws, includes fully inserting the valve into thecrimping device such that both the inflow end portion and the outflowend portion of the valve are disposed between the crimper jaws.
 13. Amethod of radially compressing a prosthetic valve, comprising: partiallyinserting the valve while in a radially expanded configuration into acrimping device comprising crimper jaws, wherein a first portion of thevalve comprises an outer skirt positioned around an outer surface of aframe of the valve that extends outside of the crimper jaws, and whereina second portion of the valve comprising the frame without the outerskirt is arranged between the crimper jaws; crimping the valve to afirst partially collapsed configuration; further inserting the valveinto the crimping device, such that the outer skirt is between thecrimper jaws; and crimping the valve to a second partially collapsedconfiguration, wherein a diameter of the valve is smaller in the secondpartially collapsed configuration than in the first partially collapsedconfiguration.
 14. The method of claim 13, further comprising crimpingthe valve to a fully collapsed configuration and wherein the diameter ofthe valve is smaller in the fully collapsed configuration than thesecond partially collapsed configuration.
 15. The method of claim 13,wherein the outer skirt comprises: an inflow edge secured to the frameat a first location; an outflow edge secured to the frame at a secondlocation, the outflow edge comprising a plurality of alternatingprojections and notches, the projections secured to the frame at thesecond location; and an intermediate portion between the inflow edge andthe outflow edge that comprises slack that buckles radially outwardsfrom the inflow and outflow edges of the outer skirt when the valve isin the radially expanded configuration.
 16. The method of claim 15,wherein crimping the valve to the first partially collapsedconfiguration includes actuating the crimper jaws such that crimper jawscontact the second portion of the valve but do not contact theintermediate portion of the outer skirt and reducing the slack in theintermediate portion of the outer skirt as the valve is crimped to thefirst partially collapsed configuration.
 17. A method of radiallycompressing a prosthetic valve, comprising: partially inserting thevalve while in a radially expanded configuration into a crimping devicecomprising crimper jaws such that a portion of the valve comprising anouter skirt extends outside of the crimper jaws, wherein the valvecomprises: a frame; and the outer skirt positioned around an outersurface of the frame, the outer skirt comprising an inflow edge securedto the frame at a first location on the frame, an outflow edge securedto the frame at a second location on the frame, and an intermediateportion between the inflow edge and the outflow edge that comprisesslack that bulges radially outwards from the inflow and outflow edges ofthe outer skirt when the valve is in the radially expandedconfiguration; crimping the valve to a first partially collapsedconfiguration such that partial flattening of the outer skirt againstthe frame occurs; further inserting the valve into the crimping device,such that the outer skirt is between the crimper jaws; and crimping thevalve to a second partially collapsed configuration such that additionalflattening of the outer skirt against the frame occurs, wherein adistance between the outflow edge and the inflow edge of the outer skirtis larger in the second partially collapsed configuration than in thefirst partially collapsed configuration.
 18. The method of claim 17,wherein when the valve is in the first partially collapsedconfiguration, the distance between the outflow edge and the inflow edgeof the outer skirt is in a range of 20% to 60% of the distance betweenthe outflow edge and the inflow edge of the outer skirt when the valveis in a fully collapsed configuration.
 19. The method of claim 17,wherein when the valve is in the second partially collapsedconfiguration, the distance between the outflow edge and the inflow edgeof the outer skirt is at least 70% of the distance between the outflowedge and the inflow edge of the outer skirt when the valve is in a fullycollapsed configuration.
 20. The method of claim 17, further comprisingcrimping the valve to a fully collapsed configuration.